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Journal of Visualized Experiments : JoVE Dec 2022There are still a limited number of primary interventions for prevention of breast cancer. For women at a high risk of developing breast cancer, the most effective...
There are still a limited number of primary interventions for prevention of breast cancer. For women at a high risk of developing breast cancer, the most effective intervention is prophylactic mastectomy. This is a drastic surgical procedure in which the mammary epithelial cells that can give rise to breast cancer are completely removed along with the surrounding tissue. The goal of this protocol is to demonstrate the feasibility of a minimally invasive intraductal procedure that could become a new primary intervention for breast cancer prevention. This local procedure would preferentially ablate mammary epithelial cells before they can become malignant. Intraductal methods to deliver solutions directly to these epithelial cells in rodent models of breast cancer have been developed at Michigan State University and elsewhere. The rat mammary gland consists of a single ductal tree that has a simpler and more linear architecture compared to the human breast. However, chemically induced rat models of breast cancer offer valuable tools for proof-of-concept studies of new preventive interventions and scalability from mouse models to humans. Here, a procedure for intraductal delivery of an ethanol-based ablative solution containing tantalum oxide nanoparticles as X-ray contrast agent and ethyl cellulose as gelling agent into the rat mammary ductal tree is described. Delivery of aqueous reagents (e.g., cytotoxic compounds, siRNAs, AdCre) by intraductal injection has been described previously in mouse and rat models. This protocol description emphasizes methodological changes and steps that pertain uniquely to delivering an ablative solution, formulation consideration to minimize local and systemic side effects of the ablative solution, and X-ray imaging for in vivo assessment of ductal tree filling. Fluoroscopy and micro-CT techniques enable to determine the success of ablative solution delivery and the extent of ductal tree filling thanks to compatibility with the tantalum-containing contrast agent.
Topics: Rats; Female; Mice; Humans; Animals; Breast Neoplasms; Ethanol; X-Rays; Contrast Media; Mastectomy; Carcinoma, Intraductal, Noninfiltrating
PubMed: 36571406
DOI: 10.3791/64042 -
International Journal of Environmental... Dec 2022A number of studies have reported breasts have high fluctuating asymmetry (FA:|Right-Left|), suggesting that they contain evolutionary and clinical information (e.g.,...
BACKGROUND
A number of studies have reported breasts have high fluctuating asymmetry (FA:|Right-Left|), suggesting that they contain evolutionary and clinical information (e.g., high FA correlates with breast cancer risk). Here we focus on breast FA in women with a wide range of breast sizes, including participants with macromastia and/or gigantomastia.
MATERIAL AND METHODS
The sample included 65 women (mean age 33.97 ± 12.1 years). Thirty were randomly selected students and/or patients who regarded their breast size as small, normal or average and who had not undergone or intended to have any breast surgery. The remainder ( = 35) were qualified for breast reduction due to macromastia and/or gigantomastia. In all participants we measured/calculated weight, height and BMI, as well as took chest photographs. Breast volumes and nipple areola complex FAs were evaluated in a specifically-designed software.
RESULTS
Breast size significantly positively correlated with breast volume FA in all women (t = 5.17, < 0.0001) and in women with macromastia/gigantomastia (t = 2.32, = 0.027). All nipple location FAs correlated positively with breast size.
CONCLUSIONS
In women with different breast sizes, breast size correlates with FA calculated from breast volume and nipple location FAs. In women with macromastia and/or gigantomastia, breasts present higher FA than "normal" breasts. This observation may give a rationale for earlier and more frequent prophylactic breast imaging in women with macromastia and/or gigantomastia.
Topics: Female; Humans; Young Adult; Adult; Middle Aged; Hypertrophy; Nipples; Mammaplasty; Mastectomy
PubMed: 36554776
DOI: 10.3390/ijerph192416895 -
Healthcare (Basel, Switzerland) Dec 2022Adolescents and young women (AYA) with breast cancer represent a unique patient population, compared to the general population with breast cancer. We performed a... (Review)
Review
Adolescents and young women (AYA) with breast cancer represent a unique patient population, compared to the general population with breast cancer. We performed a literature review to evaluate the factors that influenced the surgical outcomes in this patient population. Fifty-two studies were identified, which evaluated breast surgery type, axillary surgery, contralateral prophylactic mastectomy (CPM), surgical timing, psychological factors, disparities, and imaging use. AYA patients had equivalent oncologic outcomes with breast conserving surgery (BCS) or mastectomy. CPM did not improve survival. There are limited data on axillary management in the AYA population, and while more data would be beneficial, this is currently extrapolated from the general breast cancer population. A shorter time to initiate treatment correlated to better outcomes, and disparities need to be overcome for optimal outcomes. AYA patients appreciated involvement in clinical decisions, and shared decision making should be considered whenever possible. Providers must keep these factors in mind when counseling AYA patients, regarding the surgical management of breast cancer.
PubMed: 36554065
DOI: 10.3390/healthcare10122542 -
Cancer Aug 2022Women with PTEN Hamartoma Tumor Syndrome (PHTS) are offered breast cancer (BC) surveillance because of an increased BC lifetime risk. Surveillance guidelines are,...
BACKGROUND
Women with PTEN Hamartoma Tumor Syndrome (PHTS) are offered breast cancer (BC) surveillance because of an increased BC lifetime risk. Surveillance guidelines are, however, expert opinion-based because of a lack of data. We aimed to assess the yield and effectiveness of BC surveillance and the prevalence and type of breast disease in women with PHTS.
METHODS
Sixty-five women with PHTS who visited our center between 2001 and 2021 were included. Surveillance consisted of annual magnetic resonance imaging (MRI) and mammography from ages 25 and 30 years, respectively.
RESULTS
Thirty-nine women enrolled in the BC surveillance program (median age at first examination, 38 years [range, 24-70]) and underwent 156 surveillance rounds. Surveillance led to detection of BC in 7/39 women (cancer detection rate [CDR], 45/1000 rounds) and benign breast lesions (BBLs) in 11/39 women. Overall sensitivity (which excludes prophylactic-mastectomy detected BCs) was 100%, whereas sensitivity of mammography and MRI alone was 50% and 100%, respectively. Overall specificity was higher in follow-up rounds (86%) versus first rounds (71%). Regardless of surveillance, 21/65 women developed 35 distinct BCs (median age at first diagnosis, 40 years [range, 24-59]) and 23/65 developed 89 BBLs (median age at first diagnosis, 38 years [range, 15-61]). Surveillance-detected BCs were all T1 and N0, whereas outside surveillance-detected BCs were more often ≥T2 (60%) and N+ (45%) (p < .005).
CONCLUSIONS
The findings show that annual BC surveillance with MRI starting at age 25 years enables detection of early-stage BCs. Performance measures of surveillance and CDR were both high. BBLs were commonly present, underlining the importance of evaluation of all lesions independently.
LAY SUMMARY
Breast cancer surveillance leads to decreased tumor stage and improved survival. Breast cancer surveillance with breast magnetic resonance imaging from age 25 years onward is recommended.
Topics: Female; Humans; Adolescent; Young Adult; Adult; Middle Aged; Breast Neoplasms; Hamartoma Syndrome, Multiple; Mastectomy; Mammography; Breast; Magnetic Resonance Imaging; PTEN Phosphohydrolase
PubMed: 36533707
DOI: 10.1002/cncr.34326 -
Microbiology Spectrum Feb 2023Breast implant-associated infections (BIAIs) are the primary complication following placement of breast prostheses in breast cancer reconstruction. Given the prevalence...
Breast implant-associated infections (BIAIs) are the primary complication following placement of breast prostheses in breast cancer reconstruction. Given the prevalence of breast cancer, reconstructive failure due to infection results in significant patient distress and health care expenditures. Thus, effective BIAI prevention strategies are urgently needed. This study tests the efficacy of one infection prevention strategy: the use of a triple antibiotic pocket irrigant (TAPI) against Staphylococcus aureus, the most common cause of BIAIs. TAPI, which consists of 50,000 U bacitracin, 1 g cefazolin, and 80 mg gentamicin diluted in 500 mL of saline, is used to irrigate the breast implant pocket during surgery. We used and assays to test the efficacy of each antibiotic in TAPI, as well as TAPI at the concentration used during surgery. We found that planktonically grown S. aureus BIAI isolates displayed susceptibility to gentamicin, cefazolin, and TAPI. However, TAPI treatment enhanced biofilm formation of BIAI strains. Furthermore, we compared TAPI treatment of a S. aureus reference strain (JE2) to a BIAI isolate (117) in a mouse BIAI model. TAPI significantly reduced infection of JE2 at 1 and 7 days postinfection (dpi). In contrast, BIAI strain 117 displayed high bacterial burdens in tissues and implants, which persisted to 14 dpi despite TAPI treatment. Lastly, we demonstrated that TAPI was effective against Pseudomonas aeruginosa reference (PAO1) and BIAI strains and Together, these data suggest that S. aureus BIAI strains employ unique mechanisms to resist antibiotic prophylaxis treatment and promote chronic infection. The incidence of breast implant associated infections (BIAIs) following reconstructive surgery postmastectomy remains high, despite the use of prophylactic antibiotic strategies. Thus, surgeons have begun using additional antibiotic-based prevention strategies, including triple antibiotic pocket irrigants (TAPIs). However, these strategies fail to reduce BIAI rates for these patients. To understand why these therapies fail, we assessed the antimicrobial resistance patterns of Staphylococcus aureus strains, the most common cause of BIAI, to the antibiotics in TAPI (bacitracin, cefazolin, and gentamicin). We found that while clinically relevant BIAI isolates were more susceptible to the individual antibiotics compared to a reference strain, TAPI was effective at killing all the strains . However, in a mouse model, the BIAI isolates displayed recalcitrance to TAPI, which contrasted with the reference strain, which was susceptible. These data suggest that strains causing BIAI may encode specific recalcitrance mechanisms not present within reference strains.
Topics: Animals; Mice; Anti-Bacterial Agents; Staphylococcus aureus; Cefazolin; Breast Implants; Bacitracin; Mastectomy; Staphylococcal Infections; Polymyxin B; Gentamicins; Microbial Sensitivity Tests
PubMed: 36507629
DOI: 10.1128/spectrum.02884-22 -
Risk-reducing surgery in mutations carriers with breast cancer: a case series and literature review.Translational Breast Cancer Research :... 2022Inherited germline mutations in are known to predispose patients to a higher risk of breast, ovarian and pancreatic cancer with an estimated risk of developing breast...
BACKGROUND
Inherited germline mutations in are known to predispose patients to a higher risk of breast, ovarian and pancreatic cancer with an estimated risk of developing breast cancer in over half of all affected women by age 80 years. Current guidelines for screening patients with mutations include annual mammograms beginning at age 30 years and consideration of breast magnetic resonance imaging (MRI) and tomosynthesis. Existing evidence regarding risk-reducing surgery with mastectomy is insufficient to make a definitive recommendation to patients. In this case series, we describe the presentation and management of 5 patients with unilateral breast cancer and mutations. To our knowledge, this is the first reported case series discussing the role of contralateral risk-reducing mastectomy (CRRM) in breast cancer patients with mutations. The aim of our study was to evaluate the challenges in managing breast cancer risk in patients with pathogenic variants with illustration through real-world clinical cases and a review of the literature.
METHODS
In this retrospective observational study, we present 5 patients with mutations between the ages of 29 and 61 years who were diagnosed with breast cancer and underwent surgical management of their breast cancer at our institution between November 2020 and March 2022. Through their clinical courses and a literature review, we discuss the role of CRRM in breast cancer patients with gene mutations.
RESULTS
Out of the 5 patients, 3 patients underwent CRRM and 2 patients chose unilateral surgery for their breast cancer and active surveillance for the contralateral breast. Of the 3 patients who underwent CRRM, 1 patient experienced a surgical complication from reconstruction on the prophylactic side. None of the patients developed any recurrences with an average length of follow up of 15.4 months.
CONCLUSIONS
Based on our experience and the currently available literature, CRRM in patients with a mutation should be performed on a case-by-case basis through a shared decision-making process taking into consideration overall risk, family history, patient preference and quality of life.
PubMed: 38751533
DOI: 10.21037/tbcr-22-33 -
Breast Cancer Research : BCR Oct 2022Prediction of contralateral breast cancer (CBC) risk is challenging due to moderate performances of the known risk factors. We aimed to improve our previous risk...
BACKGROUND
Prediction of contralateral breast cancer (CBC) risk is challenging due to moderate performances of the known risk factors. We aimed to improve our previous risk prediction model (PredictCBC) by updated follow-up and including additional risk factors.
METHODS
We included data from 207,510 invasive breast cancer patients participating in 23 studies. In total, 8225 CBC events occurred over a median follow-up of 10.2 years. In addition to the previously included risk factors, PredictCBC-2.0 included CHEK2 c.1100delC, a 313 variant polygenic risk score (PRS-313), body mass index (BMI), and parity. Fine and Gray regression was used to fit the model. Calibration and a time-dependent area under the curve (AUC) at 5 and 10 years were assessed to determine the performance of the models. Decision curve analysis was performed to evaluate the net benefit of PredictCBC-2.0 and previous PredictCBC models.
RESULTS
The discrimination of PredictCBC-2.0 at 10 years was higher than PredictCBC with an AUC of 0.65 (95% prediction intervals (PI) 0.56-0.74) versus 0.63 (95%PI 0.54-0.71). PredictCBC-2.0 was well calibrated with an observed/expected ratio at 10 years of 0.92 (95%PI 0.34-2.54). Decision curve analysis for contralateral preventive mastectomy (CPM) showed the potential clinical utility of PredictCBC-2.0 between thresholds of 4 and 12% 10-year CBC risk for BRCA1/2 mutation carriers and non-carriers.
CONCLUSIONS
Additional genetic information beyond BRCA1/2 germline mutations improved CBC risk prediction and might help tailor clinical decision-making toward CPM or alternative preventive strategies. Identifying patients who benefit from CPM, especially in the general breast cancer population, remains challenging.
Topics: Humans; Female; Breast Neoplasms; Mastectomy; Prophylactic Mastectomy; Germ-Line Mutation; Risk Factors
PubMed: 36271417
DOI: 10.1186/s13058-022-01567-3 -
Journal of Plastic, Reconstructive &... Nov 2022Biological or synthetic meshes are commonly used in implant-based immediate breast reconstruction (IBR). The aim of this study was to compare patient-reported outcome... (Randomized Controlled Trial)
Randomized Controlled Trial
Are patients most satisfied with a synthetic or a biological mesh in dual-plane immediate breast reconstruction after 5 years? A randomized controlled trial comparing the two meshes in the same patient.
Biological or synthetic meshes are commonly used in implant-based immediate breast reconstruction (IBR). The aim of this study was to compare patient-reported outcome measurements (PROMs) after IBR with a synthetic mesh and a biological mesh, in a single-blinded randomized controlled trial, using the compared materials in the same patient, thereby eliminating patient-related confounders. Twenty-four patients were recruited, and all patients had a prophylactic bilateral mastectomy and a dual-plane reconstruction using anatomical breast implants. The patients' two breasts were randomized preoperatively to a biological or a synthetic mesh, using a simple approach with a parallel design. PROMs were measured with BREAST-Q. Twenty-one patients answered (88%). Most participants were equally satisfied/dissatisfied with the synthetic and the biological mesh sides regarding size of bra, softness, feel to touch, natural part of body, appearance compared with preoperatively, and palpable wrinkles, and about half of the patients regarding shape of bra, natural appearance, and visible wrinkles. The frequency of capsular contracture rate was zero in both groups at 5 years. One mesh type was not clearly superior to the other regarding PROMs, but biological and synthetic meshes seem to give rise to different types of reconstructed breasts, and more studies are needed regarding whether knowledge about the effects of different meshes can be used to tailor breast reconstructions to individual patients' wishes. The rate of complications and corrections in the biological mesh breasts was higher, and this must be considered when the type of mesh is chosen. Trial registration number: ClinicalTrials.Gov identifier NCT02985073.
Topics: Humans; Female; Surgical Mesh; Breast Neoplasms; Mastectomy; Patient Satisfaction; Mammaplasty; Breast Implants; Breast Implantation; Retrospective Studies
PubMed: 36154981
DOI: 10.1016/j.bjps.2022.08.013 -
Annals of Surgical Oncology Jan 2023Patients with clinical T4M0 breast cancer are recommended to undergo neoadjuvant chemotherapy, modified radical mastectomy, and postmastectomy radiotherapy. This study...
BACKGROUND
Patients with clinical T4M0 breast cancer are recommended to undergo neoadjuvant chemotherapy, modified radical mastectomy, and postmastectomy radiotherapy. This study determined whether BREAST-Q scores differ by decision to pursue reconstruction or timing of reconstruction.
METHODS
This retrospective, single-institutional study analyzed cT4 breast cancer patients from 2014 to 2021 without evidence of distant metastatic disease undergoing mastectomy with or without reconstruction. As routine care, BREAST-Q was administered preoperatively, then 6 months, 1 year, and 2 years postoperatively. Satisfaction and quality-of-life domains were compared between mastectomy with no reconstruction (NR), immediate reconstruction (IR), and delayed reconstruction (DR) groups.
RESULTS
Of the 144 patients eligible for this study, 71 (49%) had NR, 36 (25%) had DR, and 37 (26%) had IR. The patients undergoing reconstruction were younger and more likely to elect contralateral prophylactic mastectomy. Timing of reconstruction was not associated with significant differences in satisfaction with breasts (SATBR) at any time point. For the patients who had DR, breast satisfaction increased over time after reconstructive surgery. Physical well-being of the chest (PWB-CHEST) did not significantly differ among IR, DR, and NR at any time point. The patients who underwent DR experienced improvement in PWB-CHEST scores from preoperative scores. The patients with IR and NR experienced PWB-CHEST decline over time. Psychosocial well-being (PSWB) did not differ significantly across time or by subgroup.
CONCLUSIONS
The patients with T4 breast cancer who elected reconstruction did not differ in patient-reported outcomes based on timing of reconstruction. In the DR cohort, SATBR significantly improved after reconstructive surgery. These data can help inform breast reconstructive decision-making for patients facing the choice among DR, IR, and NR.
Topics: Humans; Female; Mastectomy; Breast Neoplasms; Retrospective Studies; Patient Reported Outcome Measures
PubMed: 36149609
DOI: 10.1245/s10434-022-12560-7 -
Journal of Surgical Oncology Jan 2023Sentinel node biopsy (SLNB) is not routinely recommended for patients undergoing prophylactic mastectomy (PM), yet omission remains a subject of debate among surgeons. A...
BACKGROUND
Sentinel node biopsy (SLNB) is not routinely recommended for patients undergoing prophylactic mastectomy (PM), yet omission remains a subject of debate among surgeons. A modern patient cohort was examined to determine occult malignancy (OM) incidence within PM specimens to reinforce current recommendations.
METHODS
All PM performed over a 5-year period were retrospectively identified, including women with unilateral breast cancer who underwent synchronous or delayed contralateral PM or women with elevated cancer risk who underwent bilateral PM.
RESULTS
The study population included 772 patients (598 CPM, 174 BPM) with a total of 39 OM identified: 17 invasive cancers (14 CPM, 3 BPM) and 22 DCIS (19 CPM, 3 BPM). Of the 86 patients for whom SLNB was selectively performed, 1 micrometastasis was identified. In the CPM cohort, risk of OM increased with age, presence of LCIS of either breast, or presence of a non-BRCA high-penetrance gene mutation, while preoperative magnetic resonance imaging was associated with lower likelihood of OM.
CONCLUSIONS
Given the low incidence of invasive OM in this updated series, routine SLNB is of low value for patients undergoing PM. For patients with indeterminate radiographic findings, discordant preoperative biopsies, LCIS, or non-BRCA high-penetrance gene mutations, selective SLNB implementation could be considered.
Topics: Humans; Female; Mastectomy; Prophylactic Mastectomy; Retrospective Studies; Breast Neoplasms; Sentinel Lymph Node Biopsy; Neoplasms, Unknown Primary
PubMed: 36069388
DOI: 10.1002/jso.27088